Although it is well known that the heart is able to increase in muscle mass in response to an increase in work load there have been relatively few studies of the cellular mechanisms responsible for this growth, their control, and relation to cardiac function. Recently, the applicant has observed that normally myosin turnover in the heart is much more rapid than in skeletal muscle. Moreover, in response to pressure overload left ventricular myosin replacement is accelerated. Additional studies are needed to delineate factors operative at the cellular level in the control of myocardial growth and their relation to cardiac function. The aims of the proposed investigation will include: (1) Studies of the metabolism of cardiac myosin and ribosomes. This will include measurements of the synthesis and degradation of the individual polypeptide chains of cardiac myosin. Similar observations will be made on the metabolism of ribosomal proteins and RNA. (2) Studies of alterations in the structure of myosin chains in hypertrophied heart. Certain aspects of the structure of myosin light and heavy chains will be examined for alterations which might explain the decrease in ATPase activity which is observed in hypertrophied and failing hearts. (3) Intracellular localization of newly synthesized myocardial proteins and RNA. Techniques similar to those used by the investigator to localize newly made myofibrillar proteins in adult skeletal muscle will be applied to heart. Also, the cell lines responsible for RNA synthesis during development of cardiac hypertrophy will be better delineated. (4) Alterations in macromolecular synthesis and degradation will be correlated with changes in cardiac function.